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What Is the Metabolic Syndrome?: Prediabetes and Cardiovascular Risk

Borgman, Marilyn RN, BSN; McErlean, Ellen MSN, RN, FAHA

The Journal of Cardiovascular Nursing: July-August 2006 - Volume 21 - Issue 4 - p 285-290
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The metabolic syndrome has been referred to as a clustering of cardiovascular risk factors, including abdominal obesity, atherogenic dyslipidemia, increased blood pressure, insulin resistance, proinflammatory state, and a prothrombotic state. The metabolic syndrome has become one of the leading clinical issues discussed by physicians and the media, leading to increased public awareness to this potentially catastrophic multiplex risk factor for cardiovascular disease. With increasing prevalence in the United States, the metabolic syndrome has been equated to cigarette smoking as a contributing factor to premature cardiovascular heart disease and one of the underlying causes of type 2 diabetes. The identification and modification of the root causes, overweight/obesity, physical inactivity, and the closely associated condition, insulin resistance, needs to be one of the initial strategies that are addressed by the clinician.

Marilyn Borgman, RN, BSN Project Manager, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio.

Ellen McErlean, MSN, RN, FAHA Project Manager, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio.

Corresponding author Marilyn Borgman, RN, BSN, Cleveland Clinic Cardiovascular Coordinating Center JJ50 9500, Euclid Ave, Cleveland, Ohio 44195(e-mail: borgmam@ccf.org).

Over the past decade, the metabolic syndrome has gone from a little-discussed entity to an established entity as one of the most prevalent combination of deadly risk factors. With increasing prevalence in the United States, the metabolic syndrome has been equated to cigarette smoking as a contributing factor to premature cardiovascular heart disease and one of the underlying causes of type 2 diabetes.1 This enhanced recognition has increased medical attention and public awareness, leading to earlier identification and intervention. The scientific community characterized the metabolic syndrome as a cluster of risk factors: glucose intolerance, insulin resistance, central obesity, dyslipidemia, and hypertension.2-4 These are all recognized contributors to coronary artery disease and diabetes. Early description of the metabolic syndrome appeared in 1980s when Vague noted that android obesity was a clinical reflection of associated factors that lead to the progression of diabetes and atherosclerosis.5 Subsequently, Reaven introduced a term for the Insulin Resistance Syndrome known as Syndrome X, a similar clustering of conditions known to be risk factors for coronary heart disease.6

There has been much discussion and many attempts made to develop a standardized clinical criterion for use in diagnosing the metabolic syndrome. The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (ATP III), the National Heart, Lung, and Blood Institute, and the American Heart Association have examined scientific issues that relate to the definition of the metabolic syndrome.2 The clinical information leading to the definition of metabolic syndrome was considered from several different perspectives: the metabolic components, major clinical outcomes, pathogenesis, clinical criteria for diagnosis, the risk for clinical outcomes, and therapeutic intervention.3

The purpose of this article is to provide an overview of the components of the metabolic syndrome, their relationship to the evolution of cardiovascular disease, and strategies for addressing these growing health risks.

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Components and Prevalence of the Metabolic Syndrome

The ATP III has identified 6 major components of the metabolic syndrome: central obesity, insulin resistance with or without glucose intolerance, an increase in blood pressure, atherogenic dyslipidemia, prothrombotic state, and proinflammatory state.3 Of these 6 components, central obesity and insulin resistance are thought to be the principal traits of the metabolic syndrome.2,3 The clinical characteristics that are typical of individuals with the metabolic syndrome are described in Table 1. These include abdominal obesity, increased triglycerides, high-density lipoprotein (HDL), hypertension, and abnormal fasting glucose. In defining the metabolic syndrome, the ATP III states that 3 of the 5 characteristics need to be present.7 Furthermore, in 1998, the World Health Organization stated that an individual would need to show evidence of insulin resistance as identified by 1 of the following: type 2 diabetes, impaired fasting glucose (IFG), or impaired glucose tolerance (IGT), in addition to at least 2 of the 4 other factors for the clinical diagnosis of metabolic syndrome2-4 (Table 2).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

Due to limited information on the prevalence of the metabolic syndrome, Drs Earl Ford, Wayne Giles, and William Dietz published findings from the Third National Health and Nutrition Examination Survey, which was conducted by the National Center for Health Statistics on more than 33,000 individuals older than 2 months from 1988 to 1994.8,9 They examined the data from the survey involving more than 8000 men and women older than 20 years in the United States following the ATP III definition of metabolic syndrome.8 The results of this report are staggering. It is estimated that 47 million or 22% of adults in the United States have the metabolic syndrome.8 The high prevalence of these foreboding risk factors escalates the importance of early detection and intervention in clinical practice and a heightened level of preventive strategies.

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Major Component of the Metabolic Syndrome: Central Obesity

Obesity in the American population has become an ever-growing problem that requires immediate attention and intervention and has a pivotal affect on the rising prevalence of the metabolic syndrome. It is estimated that 97 million adults in the United States are obese and that over half the population is overweight.3 Currently, the incidence of obesity has the potential of causing as much disease and death as does cigarette smoking.10

Obesity can substantially increase one's risk of morbidity from hypertension, type 2 diabetes, coronary artery disease, stroke, and dyslipidemia. To diagnose the presence of obesity, a variety of criteria need to be evaluated. One must look not only at the total body weight but also at the quantity of adipose tissue present. Adipose tissue is a specialized connective tissue that functions as the major storage site for fat in the form of triglycerides.11 Approximately 60% to 85% of the weight of white adipose tissue is lipid with 90% to 99% being triglyceride.11 Influencing factors for the distribution of adipose tissue are primarily genetic followed by gender. Distribution of adipose tissue that is predominantly located in the upper body area is termed "android" and is typically a characteristic of males. When adipose tissue is primarily distributed in the lower body, it is referred to as "gynoid" and is more frequently seen in women.11 Abdominal adipose tissue can be divided into subcutaneous adipose and visceral adipose tissue.12 Visceral adipocytes are more metabolically active and are recognized as a source of cytokines, resisten, adiponectin, leptin, and plasminogen activator inhibitor-1 (PAI-1), which can be potentially pathogenic.2,12 Quantifying abdominal adipose tissue can be done by a simple measure of the waist circumference13 (Fig. 1). The ATP III has identified abdominal obesity as a waist circumference of >102 cm in men and >88 cm in women.2,3 This convenient measure of abdominal adipose tissue is unrelated to height but interrelated to body mass index and total body fat.13,14 A waist circumference that is within the definition of abdominal obesity is associated with an increased risk for type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease in individuals in which the body mass index is between 25 and 34.9 kg/m.14

FIGURE 1

FIGURE 1

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Major Component of the Metabolic Syndrome: Insulin Resistance

Another major component of the metabolic syndrome is insulin resistance, although there is much debate in the clinical community whether it should be considered a primary component.2,3 It has been suggested that insulin resistance is the common denominator in developing cardiovascular disease and type 2 diabetes.7 Excessive weight, especially visceral fat accumulation with increased waist circumference, increased fasting glucose, hypertension, and dyslipidemia all have been associated with insulin resistance.15,16 Insulin resistance occurs when the normal action of insulin is impaired, leading to muscle, fat, and liver cells responding sluggishly to glucose intake.15 In this situation, the pancreas attempts to keep up with the demand for insulin by producing more, eventually allowing excessive glucose to remain in the blood.15 Individuals who have higher than the normal IFG and/or IGT but not within the diabetic range are classified as prediabetes.17 It has been shown that individuals with prediabetes will develop type 2 diabetes within 10 years.15

It is estimated that 25% of the adult population has some degree of insulin resistance.18 However, identification of insulin resistance is difficult because there are usually no associated symptoms and individuals may either have insulin resistance or prediabetes for years before it is detected. Therefore, how then is insulin resistance identified?

Detection of insulin resistance and prediabetes can be determined through fasting serum glucose levels and a glucose tolerance test. A fasting glucose of ≥110 mg/dL has been defined as prediabetes.3 This has also been referred to as IFG or IGT. At least 20 million adult Americans have IFG, IGT, or both.15 When these individuals are compared with individuals with normal blood glucose levels, they have a 1.5-fold risk of developing cardiovascular disease.19

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Major Component of the Metabolic Syndrome: Increased Blood Pressure

Another key component of the metabolic syndrome is increased blood pressure. Based on the National Health and Nutrition Examination Survey (Third National Health and Nutrition Examination Survey), 50 million Americans older than 6 years have high blood pressure, and of these, 30% are undiagnosed.20-22 Hypertension has killed 46 million Americans in the year 2001. This is an increase of 53% in the number of deaths since 1991.18 Hypertension, as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, is a systolic blood pressure of ≥140 mm Hg and a diastolic blood pressure of ≥90 mm Hg.21 Data from the Framingham Heart Study suggest that individuals that are normotensive at the age of 55 years will have a 90% lifetime risk of developing hypertension.21 Within the blood pressure range of 115/75 to 185/115, individuals between the ages of 40 and 70 years will double the risk of cardiovascular disease with each incremental increase of 20/10 mm Hg.21

In addition, there is growing recognition that individuals with increased blood pressure who do not meet the clinical definition of hypertension are also at risk, leading to the introduction of a classification for prehypertension. Prehypertension is defined as a systolic pressure of 120 to 139 mm Hg and a diastolic pressure of 80 to 89 mm Hg.21

Individuals with increased blood pressure who meet the diagnostic criteria for metabolic syndrome utilized by the ATP III would have a systolic blood pressure of ≥130 mm Hg and a diastolic blood pressure of ≥85 mm Hg.7

There is a close relationship between hypertension and cardiovascular disease which is also independent of other risk factors.21 The chances of myocardial infarction, stroke, heart failure, and renal failure are increased when hypertension is present.21,22

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Major Component of the Metabolic Syndrome: Atherogenic Dyslipidemia

Hypertriglyceridemia and a low concentration of HDL-C are defining characteristics of atherogenic dyslipidemia, another contributing component of the metabolic syndrome. Contributing factors to hypertriglyceridemia include obesity and overweight, a decrease in physical activity, an increase in alcohol intake, a high-carbohydrate diet, smoking, underlying diabetes, renal failure, and genetic disorders such as combined familial hyperlipidemia and hypertriglyceridemia.1,10 Medications such as beta blockers, estrogens, oral contraceptives, and diuretics have also affect increased triglycerides.1,10 The ATP III has established that the optimal fasting triglyceride level is <150 mg/dL. Therefore, individuals who have a fasting triglyceride level that is greater than 150 mg/dL will meet 1 of the diagnostic criteria for the metabolic syndrome.1

The second component defining atherogenic dyslipidemia is low levels of HDL-C, described by the ATP III as a level of <40 mg/dL in men and < 50 mg/dL in women.3 The Framingham Study utilizes low concentration HDL-C level as one of the factors in the scoring system to calculate the 10-year risk of coronary heart disease. Several studies that have evaluated the low levels of HDL-C to the increase risk of developing coronary heart disease demonstrated that by increasing the concentration HDL-C levels, there has been a profound reduction in major coronary events.1,2,10

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Major Component of the Metabolic Syndrome: Prothrombotic State

Prothrombotic state, or the propensity to form clots, is another key component to the metabolic syndrome.2,3 It has been identified among individuals with the metabolic syndrome that there is an increase in the tendency to develop atherothrombosis secondary to fibrinolytic dysfunction and clinical cardiovascular disease.23 This prothrombotic state is characterized by an increase in plasma PAI-1 and fibrinogen.2,3 Plasminogen activator inhibitor-1 is a single chain glycoprotein and is the primary inhibitor of tissue plasminogen activator and other plasminogen activators in the blood.24,25 The function of PAI-1 is to limit the production of plasmin, keeping fibrinolysis in check.24,25 Not only is increased PAI-1 associated with metabolic syndrome, it has also been identified as a predictor of myocardial infarctions and stroke.23 Hypertension, dyslipidemia, and hyperinsulinemia are all associated with increased PAI-1 and, as components of the metabolic syndrome, could explain why these individuals have a predisposition to develop atherothrombosis.23 The production of PAI-1 by adipose tissue could also be an important contributor to the increased plasma PAI-1 levels that are seen in insulin-resistant individuals.17

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Major Component of the Metabolic Syndrome: Proinflammatory State

The proinflammatory state is the final major component currently thought to contribute to the metabolic syndrome and is most commonly evaluated using C-reactive protein (CRP). C-reactive protein is a systemic inflammatory marker that characterizes a proinflammatory state when increased. It is thought that an increase of CRP by ≥3 mg/L is of value in predicting coronary events.1,26,27 C-reactive protein levels are characteristically increased in individuals with the metabolic syndrome.27 It has been shown that excessive adipose tissue is associated with an overproduction of proinflammatory cytokines including CRP, interleukin 6, resistin, and tumor necrosis factor α.7 As an inflammatory biomarker, CRP levels have been shown to predict myocardial infarction and stroke.27 However, it has been suggested by Miller et al that there are multiple risk factors that are irritating the coronary arteries, thus causing inflammation and leading to an increased CRP.28

There is still much to be learned about the level of risk that is associated with an increased CRP. The American Heart Association and Center for Disease Control have emphasized that CRP monitoring should be conducted at the discretion of the physician and conclude that its independent predictive value is still uncertain.2

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Strategies for Addressing the Metabolic Syndrome

Treatment of the metabolic syndrome will be addressed in greater detail later in this issue, but some basic strategies can be identified to target this growing health risk.

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Obesity

Increasing awareness of improved dietary habits needs to be the primary focus to stop the increasing incidence of obesity. Behavioral changes are needed to reduce energy intake, impact weight reduction, and increase physical activity. Clinically significant improvements, such as lower serum cholesterol and triglycerides, an increase in HDL and a decrease in blood pressure are associated with even modest weight loss.3 However, most individuals still find that changing their eating habits and weight loss is challenging.

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Insulin Resistance

Individuals older than 45 years should consider being evaluated for insulin resistance or prediabetes.15 However, in individuals who are younger than 45 years are overweight and have 1 of the following associated risk factors should be strongly advised to be evaluated for insulin resistance: have a family history of diabetes, low HDL-C, and high triglycerides; are hypertensive; or are of the African American, American Indian, Hispanic, or Asian descent.15 Care and treatment of insulin resistance lie within helping the body relearn normal use of insulin. The Diabetes Prevention Program, which was completed by the National Institutes of Health, demonstrated that individual lifestyle changes such as increasing physical activity and weight loss can reduce the risk of type 2 diabetes by 58% and a blood glucose level that returns to normal in individuals with prediabetes.15

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Hypertension

This additional classification of prehypertension allows for early intervention and education, increased public awareness, and prevention of hypertension.

Antihypertensive therapy considerations are multifactorial, including the degree of blood pressure increase, the presence of target organ damage, and the presence of coronary heart disease. In hypertensive individuals with the metabolic syndrome, no single antihypertensive agent has been identified as preferable over another.2 The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure states that most individuals will need 2 or more agents to achieve their blood pressure goal.21 However, the addition of the second agent should be initiated if after adequate dosing of a single agent fails to achieve the blood pressure goal.21 Whatever the mechanism for blood pressure control, the clinician needs to provide support and empathy to increase the individuals trust and to keep them motivated, thereby improving adherence to the therapy. In establishing the diagnosis of hypertension, the averages of 2 or more blood pressure measurements that are done on 2 or more visits after the initial screening should be used. Accuracy and consistency of blood pressure monitoring are essential to prevent missed cases of hypertension or unnecessary treatment for individuals who are not hypertensive.

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Atherogenic Dyslipidemia

Monitoring of the lipoprotein profile is essential to evaluate other lipoprotein abnormalities, including total cholesterol and LDL cholesterol that have also been shown to be atherogenic.7 It is imperative that there is an understanding of the importance of risk assessment, which can and should be the basis of therapeutic decisions and interventions. There also needs to be an understanding that differences lie within unique subsets of individuals, such as the increased risk of cardiovascular events after menopause, or that premenopausal women with diabetes do not have a reduced cardiovascular risk.10 The magnitude of reduction in the risk of cardiovascular heart disease has been conclusively documented in clinical trials. These studies demonstrated that for every 10% reduction in serum cholesterol, there would be a 15% reduction in coronary heart disease event.1 Individuals with the metabolic syndrome should adhere to a set of dietary recommendations that includes low intake of fats, cholesterol, and simple sugars, with an increase intake of fruits, vegetables, and whole grains.

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Prothrombotic State

In the metabolic syndrome, individual cardiovascular prevention is of utmost importance. Improved fibrinolytic function has the potential to reduce cardiovascular events in individuals with the metabolic syndrome. This can be accomplished by weight loss, exercise, and a controlled carbohydrate diet.3

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Proinflammatory State

Guidelines have emerged from the American Heart Association and Centers for Disease Control and Prevention for monitoring of CRP levels; these guidelines suggest that individuals who are at intermediate risk by the Framingham score, that is a 10-year risk of coronary heart disease in the range of 10% to 20%, be monitored.8 The objective in following these moderate at risk individuals is to promptly identify increased CRP levels, thereby enhancing their medical and lifestyle therapies.

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Conclusion

The metabolic syndrome is a constellation of risk factors that are individually preventable, diagnosable, and treatable. However, the metabolic syndrome is becoming one of the most prevalent diseases of humankind. When these associated metabolic abnormalities occur together, there can be an increase in the risk of developing cardiovascular disease leading to a premature death. Much more research is needed to further define the metabolic syndrome and identify applicable diagnostic techniques and effective strategies that will not only prevent the onset but also treat those already affected. Nursing has a strategic role in helping to identify the warning signs of the metabolic syndrome, thereby facilitating early education and intervention to these individuals.

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REFERENCES

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Keywords:

cardiovascular disease; insulin resistance; metabolic syndrome; type 2 diabetes

© 2006 Lippincott Williams & Wilkins, Inc.